This project will evaluate the clinical and neurohormonal effects of Angiotensin converting-enzyme (ACE) inhibition in patients with chronic heart failure due to systolic dysfunction. Endpoints of the study are variability in the response to ACE inhibitor treatment and the predictive value of the level of ACE inhibition achieved with full dose ACE inhibitor for mortality and need for adjunctive pharmacological therapy. The prospective, 4-year study will have three parts (1,2,3) in which heart failure patients naive to ACE-inhibition (1) and patients on chronic therapy (2) will be assigned in a randomized, double blind fashion to treatment with ACE-inhibitor, Angiotensin II receptor antagonist, and their combination. Withdrawal of ACE inhibitor from the combination therapy will be done to examine the respective roles of both agents in this combination (3). Measurements of functional capacity and neurohormonal activation and response to therapy will be done serially. Thus, the phenomenon of ACE escape will be substantiated or excluded. The candidate, Dr. Ulrich Jorde, is a third year fellow in Cardiology at the Albert Einstein College of Medicine and has performed preliminary research under the guidance of his mentor, Dr. Thierry H. LeJemtel. These preliminary findings will be presented at the upcoming American Heart Association Scientific Session and indicate wide variability in the response to chronic ACE inhibitor therapy, only partial ACE inhibition in the majority of heart failure patients on full dose ACE inhibitor, and potential for improvement with addition of an ARB. The data also strongly questions the existence of ACE escape. Dr. Jorde has shown a strong commitment to patient oriented clinical research and will assume the position of an Instructor in the Division of Cardiology as of 7/99 to pursue a career as an independent clinical investigator. Dr. LeJemtel, who has trained some of the most productive researchers in clinical heart failure in the United States, has agreed to continue his mentorship throughout this award. The proposal includes a two year formal training in methodology and ethics of clinical research already in place at AECOM.